The term glioma refers to tumors that are derived from normal glial cells (i.e., astrocytes, oligodendrocytes, and ependymal cells). For each of these cell types, there is a malignant counterpart (e.g., astrocytoma is derived from astrocytes). Despite significant improvements in the early detection of malignant gliomas, the median survival of patients remains less than 12 months from the time of diagnosis. Malignant gliomas rarely metastasize outside the central nervous system, but they will diffusely invade the host brain. Astrocytic tumors comprise over 80% of primary CNS tumors and are classified by the type of cell they most closely resemble and according to their clinical and biological behavior (i.e., tumor grade). The slower growing lesions are commonly referred to as low-grade gliomas (LGGs), while the more clinically aggressive tumors are classified as high-grade gliomas (HGGs). HGGs are more common comprising nearly 80% of all gliomas.
Astrocytic tumors, the most common type of neuroepithelial tissue tumors (and are therefore sometimes loosely referred to by the term “glioma”), can be further subdivided based on the severity of the condition (i.e., WHO Grade 1 to 4, based on the severity of the condition, with 4 being the most serious form of glioma). Grade 1 corresponds to pilocytic astrocytoma; Grade 2 corresponds to diffuse astrocytoma; Grade 3 corresponds to anaplastic or malignant astrocytoma; and Grade 4 corresponds to glioblastoma multiforme, which is the most common glioma in adults and is considered the most serious form of astrocytic tumor.
Treatment of CNS tumors depends on the multiplicity, location, and grade of the tumor, and may include any of surgical resection, stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT) and chemotherapy or some combination thereof; however the inability of many conventional chemotherapeutic agents to cross the blood-brain barrier (BBB) has historically limited their use in the treatment of CNS tumors. Glial tumors, the most prevalent and morbid of which is astrcoytoma and its aggressive derivative glioblastoma multiforme, are the most common cancers of the adult central nervous system. They are also among the least treatable cancers, with a 5 year survival after initial diagnosis of <10% for tumors initially diagnosed at the grade 3 (anaplastic astrocytoma) or 4 (glioblastoma) stages. The currents treatment of glioma and glioblastoma are lacking, and achieve only palliation and short-term increments in survival. They include surgical resection—following which ultimate recurrence rates are over 90%—as well as radiation therapy, and chemotherapies that include cisplatin, BCNU and other mitotic inhibitors. The benefits of these current therapies are brief and temporary, and none are curative.
Accordingly, a need remains to for more effective compositions and methods for the detection and treatment of brain tumors.